Researchers Find Biological Factors that May
Drive Prostate Tumor Aggressiveness in African-American Men

Researchers analyzing prostate tumors have identified differences
in gene expression (the degree to which individual genes are turned
on or off) between African-American and European-American men that
show the existence of distinct tumor microenvironments (the area
that includes the tumor and the surrounding non-cancerous tissue)
in these two patient groups. These findings by researchers at the
National Cancer Institute (NCI), part of the National Institute
of Health, appeared online February 1, 2008, in Cancer Research.

Many of the genes that are differentially expressed between the
tumors of African-American and European American men are related
to the immune system. The results of this study suggest that biological
differences may, in part, underlie the disparity in prostate cancer
survival rates observed between African-Americans and European-Americans.

Prostate cancer is the second leading cause of cancer-related
death among all men in the United States. However, incidence and
mortality rates for this disease vary substantially among geographic
areas and ethnic groups. Most notably, African-American men in
the U.S. have the highest risk of developing prostate cancer, and,
due to the development of more aggressive disease, they have more
than twice the mortality rate observed for other racial and ethnic
groups.

"Although preliminary, our findings are novel and could have
implications for cancer therapy," said Stefan Ambs, Ph.D.,
of NCI's Center for Cancer Research Laboratory of Human Carcinogenesis
and head of the Breast and Prostate Unit. "Our data suggest
that African-Americans and European-Americans might respond differently
to immunotherapies currently under study for prostate cancer. Understanding
the biological differences that play a role in the development
and progression of cancer among racial and ethnic groups may aid
in the development of therapies tailored to these differences."

Lead author Tiffany Wallace, Ph.D., and colleagues analyzed differences
in gene expression in prostate tumors from 33 African-American
and 36 European-American men. Their analysis revealed higher expression
of numerous genes that influence immune responses and the spread
of cancer (metastasis) in the tumors of African-American men compared
with European-American men. Among the genes with elevated expression
in prostate tumors from African-American men were genes that encode
different types of chemokines and their receptors. Chemokines are
proteins released by cells to regulate both immune system function
and cell migration. Two of these genes, CXCR4 and CCR7,
have been linked to cancer metastasis and encode proteins that
are commonly produced during inflammation and infection.

In addition, expression of a number of genes that are induced
by a cytokine called interferon was found to be elevated in the
African-American prostate tumor tissues. Interferon is produced
by cells in response to various pathogens, including viruses. This
observation suggests the possibility that viral infections could
be associated with the development of prostate tumors in African-Americans.

As part of the study, the team also analyzed the expression of
genes in non-cancerous prostate tissue from African-American and
European-American men. They found that differences in the expression
of genes related to immune system function were more prominent
in the tumor microenvironment than in non-cancerous prostate tissue.

"In future studies, we hope to investigate why gene expression
profiles in prostate tumors from African-American men contain changes
associated with immune responses. Perhaps mechanisms that block
the tumor-destroying ability of immune cells are more prevalent
in African-Americans or certain viruses are more common in African-Americans," noted
Ambs.

Having uncovered genes that were expressed at different levels
in tumors from these two ethnic populations, the researchers asked
if the converse were true: Can differences uncovered in the profiles
be used in a blind test to identify the ethnic origin of a prostate
tumor sample? The researchers identified two potential candidate
genes for successfully differentiating between tumors from African-American
and European-American men. The genes, PSPHL and CRYBB2,
were more highly expressed in the prostate tumors of African-Americans
compared with European-Americans. While little is known about the
functions of the two genes, PSPHL is located in a chromosomal
region related to advanced tumor stage in prostate cancer. Further
research is needed to determine whether PSPHL contributes
to prostate cancer.

The results from this paper suggest that prostate tumors from
African-American patients may differ in their immune biology from
those of European-American patients. "The immune-related differences
in the gene profiles could also be pointing to predisposing factors
for tumor progression and metastasis," said Ambs.

For more information about cancer, please visit the NCI website
at http://www.cancer.gov, or
call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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